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Review
. 2023 Nov;18(6):981-989.
doi: 10.1007/s11523-023-00998-y. Epub 2023 Oct 3.

Trastuzumab Deruxtecan: A Review in Gastric or Gastro-Oesophageal Junction Adenocarcinoma

Connie Kang  1
Affiliations
Review

Trastuzumab Deruxtecan: A Review in Gastric or Gastro-Oesophageal Junction Adenocarcinoma

Connie Kang. Target Oncol. 2023 Nov.

Abstract

Trastuzumab deruxtecan (Enhertu®) is a human epidermal growth factor receptor type 2 (HER2)-directed antibody-drug conjugate that is approved in several countries globally for adults with advanced HER2-positive gastric or gastro-oesophageal junction (GOJ) adenocarcinoma who have received a prior trastuzumab-based regime. In the phase II DESTINY-Gastric01 trial, intravenous trastuzumab deruxtecan was significantly more effective than standard chemotherapy (physician's choice of intravenous irinotecan or paclitaxel) in achieving objective response and improving overall survival in Japanese or South Korean adults with advanced HER2-positive gastric or GOJ adenocarcinoma who had received two or more previous therapies. In the phase II DESTINY-Gastric02 trial, trastuzumab deruxtecan was able to induce durable response in adults from the USA or Europe with unresectable or metastatic HER2-positive gastric or GOJ adenocarcinoma. Trastuzumab deruxtecan was generally tolerable in these patients; the most common adverse events included nausea, neutropenia, fatigue and decreased appetite. Trastuzumab deruxtecan carries regulatory warnings (including boxed warnings in the USA) for interstitial lung disease/pneumonitis and embryo-foetal toxicity. Current evidence indicates that trastuzumab deruxtecan is an effective treatment option, and is generally tolerable, in previously treated adults with advanced HER2-positive gastric or GOJ adenocarcinoma.

Plain language summary

Gastric or gastro-oesophageal junction (GOJ) adenocarcinomas are types of stomach cancer, which is one of the leading causes of cancer-related deaths globally. Some gastric cancers overexpress human epidermal growth factor receptor 2 (HER2), a predictor of relapse and poor survival. Management can involve several options, including surgery, chemotherapy, radiation and other systemic therapies as the first line of treatment. Trastuzumab plus chemotherapy is the standard treatment for patients with HER2-positive (HER2+) gastric or GOJ adenocarcinoma. Intravenously administered trastuzumab deruxtecan (Enhertu®) is approved in several countries for adults with advanced (spread to areas near the stomach or to other parts of the body) HER2+ gastric or GOJ adenocarcinoma who have previously received a trastuzumab-based treatment. Trastuzumab deruxtecan is cytotoxic and targets HER2-expressing tumour cells. In the DESTINY-Gastric01 trial, trastuzumab deruxtecan was significantly more effective than standard chemotherapy in achieving complete or partial responses and improving overall survival in Japanese or South Korean adults with advanced gastric or GOJ adenocarcinoma. In the DESTINY-Gastric02 trial, trastuzumab deruxtecan was able to induce confirmed (4 weeks after the initial response) complete or partial responses in adults from the USA or Europe with advanced gastric or GOJ adenocarcinoma. Trastuzumab deruxtecan was generally tolerable; the most common adverse events included nausea, decreased neutrophil count, fatigue and decreased appetite. Treatment with trastuzumab deruxtecan can lead to interstitial lung disease/lung inflammation and embryo-foetal toxicity. Current evidence indicates that trastuzumab deruxtecan is an effective treatment option, and is generally tolerable, in previously treated adults with advanced HER2+ gastric or GOJ adenocarcinoma.

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